Barzolvolimab for Chronic Urticaria

No longer recruiting at 76 trial locations

Overseen By Celldex Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Celldex Therapeutics

Must be taking: H1-antihistamines

Disqualifiers: Pregnancy, Chronic spontaneous urticaria, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 20 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called barzolvolimab (an injection) for individuals with Chronic Inducible Urticaria, a condition that causes itchy welts on the skin. The trial aims to evaluate the treatment's effectiveness, safety, and how the body processes it. Participants will receive either the barzolvolimab injection or a placebo (a harmless substance with no therapeutic effect) to compare results. This trial targets those who continue to experience symptoms despite taking H1-antihistamines and have dealt with chronic cold or symptomatic dermographism (skin writing) urticaria for at least three months. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You will need to stay on your current second generation non-sedating H1-antihistamine medication throughout the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that barzolvolimab is generally safe for individuals with chronic inducible urticaria and symptomatic dermographism. In studies, most side effects were mild and resolved over time. For those with chronic inducible urticaria, barzolvolimab proved safe and helped reduce symptoms. Similarly, for individuals with symptomatic dermographism, the treatment was well-tolerated, with mostly mild side effects.

These findings suggest that barzolvolimab is safe for humans based on the available research. However, discussing any concerns with a healthcare provider before joining a clinical trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Most treatments for chronic urticaria, like antihistamines or corticosteroids, aim to manage symptoms by reducing inflammation or blocking histamine. Barzolvolimab, however, is unique because it targets a different pathway by inhibiting the protein KIT, which plays a role in mast cell activation, a key player in chronic urticaria. Researchers are excited about barzolvolimab because it offers a novel mechanism of action that could provide relief for patients who don't respond well to existing treatments. Additionally, the subcutaneous administration every 4 to 8 weeks could offer a more convenient dosing schedule compared to daily oral medications.

What evidence suggests that this trial's treatments could be effective for Chronic Inducible Urticaria?

Research has shown that barzolvolimab may help treat Chronic Inducible Cold Urticaria and Symptomatic Dermographism. In this trial, participants will receive either barzolvolimab or a placebo. In earlier studies, 95% of patients experienced a complete response, meaning their symptoms were greatly reduced or disappeared. For Symptomatic Dermographism, up to 51% of patients had no itching or hives after 12 weeks. The treatment significantly reduced symptoms from the start of treatment to week 12. These findings suggest that barzolvolimab might be effective for people whose symptoms don't improve with antihistamines. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with Chronic Inducible Urticaria (hives) not relieved by antihistamines. Participants must have had symptoms for at least 6 weeks, use effective contraception, and be willing to maintain a symptom diary. Excluded are those with additional risky medical conditions, active infections like HIV or hepatitis B/C, other skin conditions, pregnant/nursing women, history of anaphylaxis or recent live vaccines.

Inclusion Criteria

I am willing to keep a daily electronic diary of my symptoms and attend all study visits.

I agree to use effective birth control during and for 5 months after the study.

You have a positive reaction during the skin test at both the screening and randomization visits.

Exclusion Criteria

I have a skin condition that is itchy in addition to chronic inducible urticaria.

I haven't had a live vaccine in the last 2 months and agree not to during the study.

Medical condition that would cause additional risk or interfere with study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive either barzolvolimab 150mg, 300mg, or placebo for 20 weeks

20 weeks

Subcutaneous injections every 4 or 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• barzolvolimab (CDX-0159)

Trial Overview The study tests barzolvolimab's effectiveness on hives unresponsive to H1-antihistamines. It involves comparing barzolvolimab against a placebo in terms of clinical effects and safety. The drug's behavior in the body will also be studied.

How Is the Trial Designed?

Group I: barzolvolimab 300 mg in patients with Symptomatic Dermographism Experimental Treatment 1 Intervention

barzolvolimab 300 mg injection subcutaneous every 8 weeks for 20 weeks

Group II: barzolvolimab 300 mg in patients with Chronic Inducible Cold Urticaria Experimental Treatment 1 Intervention

barzolvolimab 300 mg injection subcutaneous every 8 weeks for 20 weeks

Group III: barzolvolimab 150 mg in patients with Symptomatic Dermographism Experimental Treatment 1 Intervention

barzolvolimab 150 mg injection subcutaneous every 4 weeks for 20 weeks

Group IV: barzolvolimab 150 mg in patients with Chronic Inducible Cold Urticaria Experimental Treatment 1 Intervention

barzolvolimab 150 mg injection subcutaneous every 4 weeks for 20 weeks

Group V: Placebo Comparator in patients with Chronic Inducible Cold Urticaria Placebo Group 1 Intervention

Placebo injection subcutaneous every 4 weeks for 20 weeks

Group VI: Placebo Comparator in patients with Symptomatic Dermographism Placebo Group 1 Intervention

Placebo injection subcutaneous every 4 weeks for 20 weeks

Who Is Running the Clinical Trial?

Celldex Therapeutics

Lead Sponsor

Trials

66

Recruited

5,900+

Anthony S. Marucci

Celldex Therapeutics

Chief Executive Officer since 2008

MBA from Columbia University, MHL from Brown University

Diane C. Young

Celldex Therapeutics

Chief Medical Officer since 2019

MD from Harvard Medical School, AB in Biochemical Sciences from Harvard University

Published Research Related to This Trial

In a study of 878 French patients with chronic urticaria, omalizumab (OMA) showed a longer drug survival rate compared to previous studies, with 50% of patients still on treatment 2.4 years after starting.

The main reason for discontinuing OMA was achieving well-controlled disease in 50% of patients, but many were able to restart treatment, indicating its effectiveness in managing chronic urticaria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study. Litovsky, J., Hacard, F., Tétart, F., et al.[2023]

Barzolvolimab (CDX-0159) was well tolerated in patients with antihistamine-refractory chronic inducible urticaria, showing significant depletion of skin mast cells and reduction in serum tryptase levels, indicating effective systemic mast cell ablation.

The treatment led to complete responses in 95% of patients and significant improvements in urticaria control and quality of life, suggesting its potential as a therapeutic option for mast cell-mediated disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria. Terhorst-Molawi, D., Hawro, T., Grekowitz, E., et al.[2023]

Omalizumab 300 mg significantly reduced symptoms of chronic idiopathic urticaria (CIU) compared to placebo, with a notable decrease in urticarial activity scores and itch severity scores across multiple studies involving 1117 patients.

The treatment also increased the percentage of angioedema-free days, indicating its efficacy in managing symptoms that are resistant to conventional antihistamine treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab vs. placebo in the management of chronic idiopathic urticaria: a systematic review. Carrillo, DC., Borges, MS., García, E., et al.[2023]

Citations

1. ir.celldex.com ir.celldex.com/news-releases/news-release-details/celldex-presents-unprecedented-76-week-results-barzolvolimab

Celldex Presents Unprecedented 76 Week Results from ... Barzolvolimab also demonstrated rapid, profound complete response rates (UAS7=0; no itch/no hives) in up to 51% of patients at 12 weeks, which ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05405660?term=AREA%5BConditionSearch%5D(induction)&rank=2&checkSpell=

A Study of CDX-0159 in Patients With Chronic Inducible ... The purpose of this study is to assess the clinical effect, the pharmacodynamics, the safety, and the pharmacokinetics of barzolvolimab (CDX-0159) in patients ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36385701/

Anti-KIT antibody, barzolvolimab, reduces skin mast cells ... Complete responses (negative provocation test) occurred in 95% (n = 19/20) of patients (n = 10/10 ColdU; n = 9/10 SD), and all (n = 20/20) showed improvement in ...

4. ir.celldex.com ir.celldex.com/news-releases/news-release-details/celldex-presents-data-demonstrating-barzolvolimab-improves

Release Details Barzolvolimab achieved the primary efficacy endpoint of the study—a statistically significant mean change from baseline to week 12 in UAS7 ( ...

5. annallergy.org annallergy.org/article/S1081-1206(24)01565-5/fulltext

Positive efficacy and favorable safety of barzolvolimab in ... The study met the primary endpoint with unprecedented, clinically meaningful, and statistically significant complete response rates (negative provocation test) ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1081120624015655

Positive efficacy and favorable safety of barzolvolimab in ... This phase II barzolvolimab study is the first large, randomized placebo-controlled study to achieve a successful outcome for CIndU.

7. ir.celldex.com ir.celldex.com/news-releases/news-release-details/celldex-announces-barzolvolimab-met-all-primary-and-secondary

Celldex Announces Barzolvolimab Met All Primary and ... Barzolvolimab is the first drug to achieve success in a large, randomized, placebo-controlled study in chronic inducible urticaria.

8. healio.com healio.com/news/allergy-asthma/20241106/chronic-inducible-urticaria-improves-in-12-weeks-with-barzolvolimab

Chronic inducible urticaria improves in 12 weeks with ... Positive efficacy and favorable safety of barzolvolimab in chronic inducible urticaria: Phase 2 trial results. Presented at: ACAAI Annual ...